Comparative proteomic analysis of histone post-translational modifications upon ischemia/reperfusion-induced retinal injury

Xiaolu Zhao, Simone Sidoli, Leilei Wang, Wenjun Wang, Lin Guo, Ole N. Jensen, Ling Zheng

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

We present a detailed quantitative map of single and coexisting histone post-translational modifications (PTMs) in rat retinas affected by ischemia and reperfusion (I/R) injury. Retinal I/R injury contributes to serious ocular diseases, which can lead to vision loss and blindness. We applied linear ion trap-orbitrap hybrid tandem mass spectrometry (MS/MS) to quantify 131 single histone marks and 143 combinations of multiple histone marks in noninjured and injured retinas. We observed 34 histone PTMs that exhibited significantly (p < 0.05) different abundance between healthy and I/R injured eyes, of which we confirmed three H4 histone marks by Western blotting. H4K20me2 was up to 4-fold change up-regulated after the injury and is associated with the response to DNA damage as demonstrated by an increase in the phosphorylation of p53 and Chk1. This study demonstrates that quantitative MS provides a sensitive and accurate way to dissect the changes in the histone code after retinal injury. Specifically, DNA damage associated histone PTMs may contribute to neurovascular degeneration during the process of ischemia/reperfusion injury.

Original languageEnglish (US)
Pages (from-to)2175-2186
Number of pages12
JournalJournal of Proteome Research
Volume13
Issue number4
DOIs
StatePublished - Apr 4 2014
Externally publishedYes

Keywords

  • DNA damage
  • LC-MS/MS
  • PTMs
  • histones
  • ischemia/reperfusion injury
  • label-free quantitation
  • retina

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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